Tonin, a new enzyme which forms angiotensin II directly from angiotensinogen, is present in most tissues and is in relatively higher concentrations in the submaxillary gland and in the inner cortex and outer medulla of the kidney. This enzyme has been obtained in a homogeneous form, crystallized, and the N-terminal sequence of the first 34 amino acids identified. Active and passive immunization against tonin decreases the blood pressure in one-kidney, one-clip renovascular hypertension. We propose: (1) to determine whether tonin plays a role in the pathogenesis of different types of hypertension; (2) to determine the subcellular and cellular localization of tonin in the submaxillary gland, kidney and other tissues; (3) to determine the effect of chronic infusion of tonin on blood pressure, plasma renin activity (PRA), plasma aldosterone concentration, and renal function; (4) to determine whether tonin increases blood pressure by releasing a new pressor peptide or substance other than angiotensin II, since tonin increases blood pressure in rats treated with an angiotensin antagonist; and (5) to determine whether isolated perfused kidneys release tonin in the vascular compartment and what factors control this release. These studies are important because they will increase our understanding of a new mechanism which may participate in the pathogenesis of hypertension. The previous work on tonin, with the exception of that on its crystallization, has been done by only one group of investigators, J. Genest and R. Boucher (Montreal, Canada).